Site-specific dephosphorylation of doublecortin (DCX) by protein phosphatase 1 (PP1)

Shmueli, Anat; Gdalyahu, Amos; Sapoznik, Sivan; Sapir, Tamar; Tsukada, Miki; Reiner, Orly

doi:10.1016/j.mcn.2006.01.014

Cited by 48 publications

(51 citation statements)

References 47 publications

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“…6A). These data are consistent with those of Shmueli et al (31). These data show that the conserved KVRF motif and JNK sites in DCX are responsible for association of neurabin II and PP1 with DCX.…”

Section: Resultssupporting

confidence: 93%

“…6B-D). Human embryonic kidney cells HEK 293 are a neurabin II null cell line (31). Deficiency of neurabin II expression in HEK 293 cells is also confirmed in Western blot analysis (Fig.…”

Section: Resultsmentioning

confidence: 53%

“…Native neurabin II associates with PP1 (44). DCX, neurabin II, and PP1 are found in the same protein complex when PP1 is pulled down with PP1-specific microcystin-agarose beads and also when DCX is immunoprecipitated from mouse brain extracts (31). Our data show that JNK inhibitors and JNK site-directed mutagenesis (T331, S334) in DCX reduced the interaction between DCX and neurabin II in glioma cells and JNK activation by MKK7-JNK1, and increased DCX phosphorylation and its interaction with neurabin II in glioma cells.…”

Section: Discussionmentioning

confidence: 97%

“…Our data show that JNK inhibitors and JNK site-directed mutagenesis (T331, S334) in DCX reduced the interaction between DCX and neurabin II in glioma cells and JNK activation by MKK7-JNK1, and increased DCX phosphorylation and its interaction with neurabin II in glioma cells. Phosphatase inhibitors reduce the interaction between DCX and neurabin II and also inhibit DCX-neurabin II-PP1 complex formation (31). Thus, phosphorylation and dephosphorylation both may be required for interaction between DCX and neurabin II and DCX-neurabin II-PP1 complex formation.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, phosphorylation and dephosphorylation both may be required for interaction between DCX and neurabin II and DCX-neurabin II-PP1 complex formation. Interaction between phosphorylated DCX and neurabin II induces association of DCX, neurabin II, and PP1 in vivo (31). PP1, one of the key eukaryotic serine/threonine protein phosphatases, is involved in the mitotic dephosphorylation of pRb (reviewed in ref.…”

Section: Discussionmentioning

confidence: 99%

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Ectopic Doublecortin Gene Expression Suppresses the Malignant Phenotype in Glioblastoma Cells

Santra¹,

Zhang²,

Santra³

et al. 2006

Cancer Research

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Doublecortin (DCX) is one of the three genes found from Affymetrix gene chip analysis related to glioma patient survival. Two other genes (e.g., osteonectin and semaphorin 3B) are well characterized as antioncogenic and tumor suppressor genes. However, there is no report about the involvement of DCX in cancer. Here, we show that gene transfer technology into DCX-deficient glioblastoma cell lines, such as A172, U87, U251N, RG2, and 9L, with DCX cDNA significantly suppressed growth of these glioma cells. U87 cells with ectopic expression of DCX exhibit a marked suppression of the transformed phenotype as growth arrested in the G 2 phase of the cell cycle progression, small colony formation in soft agar, and no tumor formation in nude rats. This transformed phenotype can be restored by knocking down DCX expression with DCX small interfering RNA. DCX was highly phosphorylated in glioma cells. Phosphorylation in the glioma cells was greater than in noncancer cells such as mouse NIH 3T3 and human embryonic kidney 293T cells. Coimmunoprecipitation of the phosphorylated DCX and spinophilin/neurabin II from DCX-synthesizing glioma cells indicated their interaction. This interaction would lead to a block of anchorage-independent growth as neurabin II is a synergistic inhibitor of anchorage-independent growth with p14ARF (ARF). Interaction between phosphorylated DCX and neurabin II may induce the association of the protein phosphatase 1 catalytic subunit (PP1) with neurabin II and inactivate PP1 and block mitosis during G 2 and M phases of the cell cycle progression. Thus, DCX seems to be a tumor suppressor of glioma. (Cancer Res 2006; 66(24): 11726-35)

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Section: Resultssupporting

confidence: 93%

“…6B-D). Human embryonic kidney cells HEK 293 are a neurabin II null cell line (31). Deficiency of neurabin II expression in HEK 293 cells is also confirmed in Western blot analysis (Fig.…”

Section: Resultsmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Ectopic Doublecortin Gene Expression Suppresses the Malignant Phenotype in Glioblastoma Cells

Santra¹,

Zhang²,

Santra³

et al. 2006

Cancer Research

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The role of Rho GTPase proteins in CNS neuronal migration

Govek

Hatten

Aelst

2011

Developmental Neurobiology

149

137

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The architectonics of the mammalian brain arise from a remarkable range of directed cell migrations, which orchestrate the emergence of cortical neuronal layers and pattern brain circuitry. At different stages of cortical histogenesis, specific modes of cell motility are essential to the stepwise formation of cortical architecture. These movements range from interkinetic nuclear movements at the ventricular zone (VZ), to migrations of early-born, postmitotic polymorphic cells into the preplate, to the radial migration of precursors of cortical output neurons across the thickening cortical wall, and the vast, tangential migrations of interneurons from the basal forebrain into the emerging cortical layers. In all cases, acto-myosin motors act in concert with cell adhesion receptor systems to provide the force and traction needed for forward movement. As key regulators of actin and microtubule cytoskeletons, cell polarity, and adhesion, the Rho GTPases play a critical role in CNS neuronal migration. This review will focus on the different types of migration in the developing neocortex and cerebellar cortex, and the role of the Rho GTPases, their regulators and effectors in these CNS migrations, with particular emphasis on their involvement in radial migration.

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Structural characterization of the neurabin sterile alpha motif domain

Ragusa

Hudak

et al. 2007

Proteins

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Site-specific dephosphorylation of doublecortin (DCX) by protein phosphatase 1 (PP1)

Cited by 48 publications

References 47 publications

Ectopic Doublecortin Gene Expression Suppresses the Malignant Phenotype in Glioblastoma Cells

Ectopic Doublecortin Gene Expression Suppresses the Malignant Phenotype in Glioblastoma Cells

The role of Rho GTPase proteins in CNS neuronal migration

Structural characterization of the neurabin sterile alpha motif domain

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